An effective method for introducing peptides into the brain.
Administration of synthetic or purified peptides directly into the brain ventricles is a method commonly used by neuroscientists for exploring physiological and behavioral functions of gene products. Intra-ventricle administration is controlled by the blood–brain barrier, which limits its effectiveness, and currently available methods for the delivery of peptides or pharmacological agents into the cerebrospinal fluid (CSF) in the brain present researchers with limitations, concerning both the natural properties of the delivered substance (solubility, stability, synthesis, purifications, etc) and the experimental needs (prolonged and/or repeated administration, inducible delivery, minimal handling of the experimental animals, etc). The current technology utilizes a genetic approach for the specific delivery of secreted peptides or proteins into the CSF.
The choroid plexus is a blood–CSF barrier, composed of epithelial cells, that plays a critical role in the mechanism regulating the exchange of molecules between the brain’s internal milieu and the periphery. Neuromodulators directed to CSF can modify and adapt a variety of behavioral, neuroendocrine, and immunologic processes. The proposed technology is a lentiviral-based system which uses a choroid plexus specific promoter. The functionality of this system was demonstrated by using the over-expression of the two established neuropeptides. This technology may prove as a powerful tool for addressing research questions involving acute or chronic effects of gene products within the CNS.